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M Taningher

Publications and source records attributed to M Taningher.

62 records · Page 4Linked to original sources
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Predictive ability of the autoradiographic repair assay in rat liver cells compared with the Ames test.

Data from the literature for 25 compounds belonging to different chemical classes were collected and their potency in the autoradiographic repair assay in rat liver cells was compared with their carcinogenic potency. A very modest correlation was found between the two parameters (r = 0.36). For 21 of the compounds it was also possible to compare mutagenic potency in the Ames test with carcinogenic potency. Even in this case the correlation was low (r = 0.40). The results are compared with those of previous studies of different short-term tests used to predict carcinogenic potency.

Animals↗
PubMedDate not supplied

Quantitative predictivity of the transformation in vitro assay compared with the Ames test.

For 59 chemical compounds, we have found homogeneous data on transformation in vitro, mutagenicity in the Ames test, and carcinogenicity. We have compared the potency in inducing transformation in vitro in hamster fibroblast cells with the carcinogenic potency and found a modest correlation coefficient between the two parameters (r = 0.37). For these same 59 compounds it was also possible to compare mutagenic potency in the Ames test with carcinogenic potency. The correlation level was very similar (r = 0.34). The predictivity of transformation in vitro increased significantly when only compounds for which some kind of dose-response relationship was available were utilized (r = 0.65). This result stresses the importance of the quantitative aspect of the response in predictivity studies. The present study is compared with previous studies on the quantitative predictivity of different short-term tests. Our work is not definitive, but gives an idea of the possible type of approach to the problem of comparing quantitative predictivities.

Animals↗
PubMedDate not supplied

Alkaline DNA fragmentation in vivo: borderline or negative results obtained respectively with 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene.

Using the in vivo DNA damage alkaline elution assay, a satisfactory correlation with carcinogenicity in the same target organ has been previously shown for a variety of chemical agents. This work was intended to enlarge the exploration of the predictivity of this test. Benzo[a]pyrene (BP) was found negative for damage to liver DNA of mice and rats, and 7,12-dimethylbenz[a]anthracene (DMBA) negative for damage to liver and bone marrow DNA of mice and slightly positive for damage to mammary gland DNA of young female rats. The results were found to be correlated with the extension of DNA arlyation in target organs in similar experimental conditions. From carcinogenicity data reported in the Survey of Compounds Which Have Been Tested for Carcinogenic Activity (vols. 1961-1973) BP and DMBA were both found to be essentially negative as liver carcinogens; however, DMBA was a potent carcinogen in inducing mammary tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

A procedure for the assay of DNA damage in mammalian cells by alkaline elution and microfluorometric DNA determination.

The microfluorimetric assay of Kissane and Robins (J. Biol. Chem. 233, 184-188, 1958) has been modified to monitor DNA content in alkaline elution fractions. The elution profiles of DNA from treated and control cultured cells demonstrated a good correlation whether DNA in the elution fractions was determined by the fluorometric method or by measuring its radioactivity. The DNA recovery was of about 80% and the measured material was DNase digestible.

Cell Line↗
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Major discrepancies between results obtained with two different methods for evaluating DNA damage: alkaline elution and alkaline unwinding. Possible explanations.

The fluorometric assay of DNA alkaline unwinding, developed by Birnboim and Jevcak (Cancer Res 41: 1889-1892, 1981) was applied to rat liver DNA, after treatment in vivo. N-nitrosodimethylamine, for which DNA damage in rat liver has been extensively investigated, was tested as a standard compound. The results were in complete agreement (both in terms of damage and repair) with data from the literature and with our own results obtained with other methods of detecting DNA alkaline fragmentation. Sensitivity was also of the same order of that of usual methods, with the effect of 0.3 mg/Kg of N-nitrosodimethylamine being detectable. Other DNA damaging carcinogens such as 1,2-dimethylhydrazine, 2-naphthylamine and dacarbazine were also correctly detected. Compounds like nitrofurantoin, benzoin and caprolactam, which appeared clearly positive with the alkaline elution technique, but for which genotoxicity and carcinogenicity are doubtful (nitrofurantoin) or most likely negative (benzoin and caprolactam), gave negative results with this method. This is also in agreement with previous results, observed using a different approach to measuring DNA unwinding. On the basis of these and other observations, we suggest that, under certain conditions, the alkaline elution technique is perhaps not only sensitive to DNA breaks but also to changes in chromatin conformation. Unwinding methods could be more specific in the detection of DNA fragmentations.

Animals↗
PubMedDate not supplied

Induction of preneoplastic nodules: quantitative predictivity of carcinogenicity.

Using data from two independent studies, the quantitative predicitivity of carcinogenicity of the liver preneoplastic nodules test was examined. It was compared with the predicitivity of two short-term parameters: the Ames test and acute toxicity. In analyzing the results of both studies, a rather high quantitative predictivity was shown for the preneoplastic nodules (r = 0.43 and r = 0.60, respectively). For one study, the predictivity was approximately of the same order as the internal consistency of the carcinogenicity data (median r = 0.69). The preneoplastic nodules were more predictive than the Ames' test as a statistical trend. The predictivity of the Ames' test has been found to be rather poor; especially in one case where r = 0.10. As expected, acute toxicity was the less predictive short-term parameter.

Animals↗
PubMedDate not supplied

Evidence for a fast repair of apurinic sites induced by N-nitroso-dimethylamine in rat liver DNA.

Sprague Dawley male rats were treated with N-nitroso-dimethylamine and the damage induced in liver DNA was investigated using the in vivo DNA alkaline elution assay. Determination of the number of single stranded breaks after different incubation periods in alkali showed that most of them (approximately equal to 95%) were alkali-labile sites, with a half-life of about 33 min, as expected for apurinic sites. The extent of DNA methylation was calculated, by assuming depurination of N-7-methylguanine to be the rate-limiting step for breakdown of DNA. The amount of DNA fragmentation observed accounted for only one fifth of N-7-methylguanine. The calculation could be made to correspond to the extent of methylation determined experimentally, by assuming the occurrence of a fast repair in vivo of apurinic sites (t1/2 approximately equal to 18 min). Our hypothesis of a fast repair of apurinic sites is in agreement with the analysis of data of Peterson et al. (1974). Moreover, the rate of repair required by the level of spontaneous depurination of normal guanine at neutral pH and 37 degree C, agrees satisfactorily with our estimations.

Animals↗